Role of caprin-1 in carcinogenesis

Abstract

RNA-binding proteins serve an essential role in post-transcriptional gene regulation. Cytoplasmic activation/proliferation-associated protein-1 (caprin-1) is an RNA-binding protein that participates in the regulation of cell cycle control-associated genes. Caprin-1 acts alone or in combination with other RNA-binding proteins, such as RasGAP SH3-domain-binding protein 1 and fragile X mental retardation protein. In the tumorigenesis process, caprin-1 primarily functions by activating cell proliferation and upregulating the expression of immune checkpoint proteins. Through the formation of stress granules, caprin-1 is also involved in the process by which tumor cells adapt to adverse conditions, which contributes to radiation and chemotherapy resistance. Given its role in various clinical malignancies, caprin-1 holds the potential to be used as a biomarker and a target for the development of novel therapeutics. The present review describes this newly identified putative oncogenic protein and its possible impact on tumorigenesis.

Keywords: RNA-binding proteins; cytoplasmic activation/proliferation-associated protein-1; epigenetics; tumorigenesis.

Figure 1.

RNA granules and caprin-1-associated tumorigenesis. Caprin-1 mRNA is produced in the nucleus and transported into mRNP or the SG through the transport granule, and finally degraded in the P-body. Caprin-1-associated tumorigenesis takes place primarily through affecting SG-mediated tumorigenic characteristics and the MYC-mediated immune checkpoint. eIF2α can be activated by various stress stimuli and induces SG formation, thereby leading to tumorigenic characteristics, such as increased transition from the G₁ to the S phase of the cell cycle, increased Ras signaling pathway, EMT and decreased apoptosis. Caprin-1 can also indirectly enhance the expression of immune checkpoint proteins, such as CD47 and PD-L1, through MYC, which is one of the regulatory targets of caprin-1. Caprin-1, cytoplasmic activation/proliferation-associated protein-1; mRNP, mRNA protein complexes; SG, stress granule; P-body, processing body; eIF2α, eukaryotic translation initiation factor 2α; EMT, epithelial to mesenchymal transition; PD-L1, programmed death-ligand 1; TIA-1, T-cell-restricted intracellular antigen-1; TTP, tristetraprolin; mTORC1, mammalian target of rapamycin complex 1; DCP, decapping enzyme; Ago2, argonaute 2; G3BP, GTPase-activating protein (Src homology 3 domain) binding protein; FMRP, fragile X mental retardation 1.